Biomedical subjects

M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 19 recordsLinked to original sources

PubMed2007

Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients--a double-blind, randomized study.

BACKGROUND: Classical hormone replacement therapy for hot flashes is contraindicated in breast cancer especially in endocrine responsive disease. PATIENTS AND METHODS: In a double-blind, randomized phase III study, breast cancer patients suffering from hot flashes at least twice a day, who were not taking any medication against hypertension and depression received either clonidine 0.075 mg twice a day or venlafaxine 37.5 mg twice a day for 4 weeks. The primary end point was defined as the frequency of hot flashes after 4 weeks of treatment. A self-reported 1-week hot flash and other symptom questionnaire were kept before the start of treatment until the end of treatment course. RESULTS: From April 2002 to October 2004, 80 patients were recruited of whom 64 were assessable for efficacy analyses. Thirty-three received clonidine and 31 venlafaxine, nine patients stopped early because of side-effects and seven withdrew consent. At the end of treatment week 4, the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes per day for those receiving clonidine (P = 0.025). CONCLUSION: Venlafaxine is significantly more effective in reducing the frequency of hot flashes in breast cancer patients than clonidine.

Adult↗

PubMed2006

Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response.

Gene expression analysis in breast cancer patients undergoing neoadjuvant chemotherapy is an interesting tool for identification of gene signatures and new markers to predict tumor response. However, the detection of predictive markers strongly depends on the drugs used in the specific therapeutic setting. There is growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for anthracycline-, and microtubule-associated protein tau (MAPT) for taxane sensitivity. HER-2 has been described as a marker of both anthracycline and taxane sensitivity. We performed gene expression profiling of 50 patients within the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial. Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA expression for pathological complete response (pCR) in this setting. Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as well as overall response (P=0.037) and clinical complete response (cCR, P=0.050). In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed in our sample group.

Adult↗

PubMed2006

Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL).

INTRODUCTION: Sequential high dose (SHiDo) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. METHODS: To confirm this result in a multicenter trial, we randomized patients with aggressive NHL, to receive either eight cycles of CHOP or SHiDo. The primary endpoint was overall survival. RESULTS: 129 evaluable patients were randomized to receive either CHOP or SHiDo: median age, 48 years; 62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3: 21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13% versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2% with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial remissions, respectively. After a median observation time of 48 months, there was no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP (P = 0.48). CONCLUSION: In this multicenter trial, early intensification with SHiDo did not confer any survival benefit in previously untreated patients with aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.

Adolescent↗

PubMed2006

Uterotubal transport disorder in adenomyosis and endometriosis--a cause for infertility.

OBJECTIVE: Uterine hyperperistalsis and dysperistalsis are common phenomena in endometriosis and may be responsible for reduced fertility in cases of minimal or mild extent of disease. Since a high prevalence of adenomyosis uteri has been well documented in association with endometriosis, we designed a study to examine whether hyperperistalsis and dysperistalsis are caused by the endometriosis itself or by the adenomyotic component of the disease. DESIGN: A prospective observational study. SETTING: University hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 300 in vitro fertilisation/intracytoplasmatic sperm injection cycles and 350 intrauterine insemination cycles/year. POPULATION: Forty-one subjects with infertility and with laparoscopically proven endometriosis and patent fallopian tubes. Thirty-five subjects (85%) additionally showed signs of adenomyosis. METHODS: All subjects underwent T2-weighed magnetic resonance imaging (MRI) and hysterosalpingoscintigraphy (HSSG) during the subsequent menstrual cycle. MRI revealed the extent of the adenomyotic component of the disease and the integrity of uterotubal transport capacity was evaluated by HSSG. MAIN OUTCOME MEASURES: Influence of adenomyosis on uterotubal transport capacity in endometriosis. RESULTS: In 35 of the 41 subjects (85%) with endometriosis, signs of adenomyosis were detected using T2-weighed MRI. Two of six (33%) subjects with no adenomyosis (group I) showed dysperistalsis and hyperperistalsis, compared with 14 of 24 (58%) women with focal adenomyosis (group II) and 10 of 11 (91%) women with diffuse adenomyosis (seven showed a failure in transport capacity and two contralateral transport). CONCLUSIONS: Our data suggest that endometriosis is associated with impeded hyperperistaltic and dysperistaltic uterotubal transport capacity. However, adenomyosis is of even more importance, especially when diffuse adenomyosis is detected. Both forms of adenomyosis are commonly found in subjects with mild to moderate endometriosis. We suggest that the extent of the adenomyotic component in subjects with endometriosis explains much of the reduced fertility in subjects with intact tubo-ovarian anatomy.

Adenomyoma↗

PubMed2006

Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo.

Cyclin B1 is the regulatory subunit of cyclin-dependent kinase 1 (Cdk1) and is critical for the initiation of mitosis. Accumulating data indicate that the deregulation of cyclin B1 is tightly linked to neoplastic transformation. To study the phenotype and the potential preclinical relevance, we generated HeLa cell lines stably transfected with the plasmids encompassing short hairpin RNA (shRNA) targeting cyclin B1. We demonstrate that the reduction of cyclin B1 caused inhibition of proliferation by arresting cells in G2 phase and by inducing apoptosis. Cells, entering mitosis, were impaired in chromosome condensation and alignment. Importantly, HeLa cells with reduced cyclin B1 were more susceptible to the treatment of small interfering RNA targeting Polo-like kinase 1 (Plk1) and to the administration of the chemotherapeutic agent taxol. Finally, HeLa cells with reduced cyclin B1 showed inhibited tumor growth in nude mice compared to that of control cells. In summary, our data indicate that cyclin B1 is an essential molecule for tumor cell survival and aggressive proliferation, suggesting that the downregulation of cyclin B1, especially in combination with other molecular targets, might become an interesting strategy for antitumor intervention.

Animals↗

PubMed2006

[Significance of Escherichia coli O157 in sheep at slaughter in Switzerland].

The importance of latent zoonoses has increased in recent years in view of foodborne diseases: (i) the "healthy" animal repesents a reservoir for specific pathogens; () no pathological-anatomical changes in the carcass and its organs show the presence of these pathogens; and (iii) these pathogens may enter the food chain via hygienic weak points in the slaughtering process. To estimate the risks involved and to take appropriate measures, analysis of the slaughtering process should be complemented by collecting data relating to the carriage of the animals of latent zoonotic pathogens. From October 2004 to June 2005, fecal samples from 630 slaughtered sheep were enriched and then examied by IMS technique and by PCR to assess the prevalence of E. coli O157 (OE). Seven samples (1.1%), distributed throughout the whole examination period, were found to be positive. To assess the potential pathogenicity for humans, E. coli O157 strains were isolated by colony hybridization and further characterized. The isolated strains fermented Sorbitol, showed four different H tys (H7, H12, H38, H48), and were all negative for stx. One O157:H7 strain harbored the gene for intimin (eae) in combination with ehxA, and paa. In consequence, the potential health hazard from sheep meat related to O157 STEC seems current not to be of particular importance in Switzerland. Results emphasize the fact that E. coli O157 are not always STEC but may belong to other pathotypes as nontraditional EPEC.

Abattoirs↗

PubMed2006

[Qualification and education in gynecological oncology].

The German Medical Association (Bundesärztekammer) has launched a new organisational structure in the curriculum of medical qualification. Beside the field of obstetrics and gynecology this has led to three specialisation. The newly established specialisation is that of gynecological oncology. Therewith in the future the treatment and care for women with genital or breast cancer will be focused to those centers having the necessary qualification. In addition the German qualification is identical to that of the European Society of Gynecological Oncology (ESGO). So German fellows can obtain a national and international qualification at qualified centers.

Clinical Competence↗

PubMed2006

[Adjuvant therapy with trastuzumab (Herceptin) in primary breast cancer].

The results of four randomized international multicentric trials evaluating the therapeutic benefit of Herceptin in the adjuvant treatment of HER2-neu positive primary breast cancer have been reported. These reports showed that even after short term follow up one year of Herceptin resulted in improved disease free, metastases free and overall survival. Design and results of these four studies and the recommendations of national and international societies for the use of Herceptin in the adjuvant setting will be discussed.

Antibodies, Monoclonal↗

PubMed2006

[Clinical management of an androgen insensitivity syndrome].

The seldom occurring androgen insensitivity syndrome is characterised by male karyotype in a phenotypical women. We report on a complete androgen insensitivity syndrome with the rare coincidence of bilateral Fallopian tubes and a testicular intraepithelial neoplasia. Additionally we discuss aspects of incidence, molecular background, characteristics, diagnostic pitfalls and therapy against the background of the current literature.

Adolescent↗

PubMed2006

Gene expression profiles of breast cancer obtained from core cut biopsies before neoadjuvant docetaxel, adriamycin, and cyclophoshamide chemotherapy correlate with routine prognostic markers and could be used to identify predictive signatures.

BACKGROUND: Neoadjuvant administration of chemotherapy provides a unique opportunity to monitor response to treatment in breast cancer and assesses response exactly. Global gene expression profiling by microarrays has been used as a valuable tool for the identification of prognostic and predictive marker genes. Even though this technology is now wide spread and relatively standardized, there are only few data available which compare established parameters with expression values to determine reliability of this method. Therefore we analyzed gene expression data of pretreatment biopsies of breast cancer patients and compared them with the results of the immunohistochemical receptor expression for ER/ PR and Her-2, as well as FISH testing for HER-2 amplification. We analyzed the change of expression of these markers before and after neoadjuvant chemotherapy. Furthermore we evaluated the predictive significance of prognostic gene signatures as described by Sorlie, van't Veer and Ahr for response to neoadjuvant chemotherapy. METHODS: Pretherapeutic core biopsies were obtained from 70 patients undergoing neoadjuvant TAC chemotherapy within the GEPARTRIO-trial. Samples were characterized according to standard pathology including ER, PR and HER2 IHC and amount of cancer cells. Only biopsies with more than 80 % tumor cells were considered for further examination. RNA was isolated and expression profiling performed using Affymetrix Hg U133 Arrays (22 500 genes). GeneData's Expressionist software was used for bioinformatic analyses. RESULTS: More than two thirds of the biopsies yielded sufficient amounts (> 5 microg) of RNA for expression profiling and high quality data were obtained for 50 samples. Unsupervised clustering broadly revealed a correlation with hormone receptor status. When ER-alpha, PR and HER2 as analyzed by immunohistochemistry were compared to the corresponding mRNA data from gene chips more than 90 % concordance was observed. We could observe a switch of receptor expression for ER, PR or HER-2 from positive to negative and vice versa in 16/35 cases (45.7 %) and 5/22 cases (22.7 %) respectively. The prognostic marker sets of Sorlie, van't Veer and Ahr could not discriminate responders from non-responders in our patient group. CONCLUSIONS: Our results demonstrate that reliable expression profiles can be achieved by using limited amounts of tissue obtained during neoadjuvant chemotherapy. Microarray data capture conventional prognostic markers but might contain additional informative gene sets correlated with treatment outcome. Prognostic marker sets are not suitable to predict tumor response in the neoadjuvant setting, suggesting the necessity of class prediction methods to identify marker sets predictive for the type of therapy used.

Adult↗

PubMed2006

[Integrin expression in eutopic and ectopic endometrium].

The significance of retrograde menstruation as a risk factor for endometriosis has been confirmed by numerous clinical observations. Integrins mediate both cell-cell and cell-matrix adhesion, and it is therefore suspected that integrins are involved in the development of endometriosis. Using immunohistochemistry, integrin expression in eutopic and ectopic endometrium is examined in endometriosis patients and control individuals. In nearly all cases, the glandular epithelial cells in the endometrium showed expression of alpha (2-), alpha (3)-, alpha (6)- and alpha (v)- integrin and a low percentage of expression of alpha (1)-, alpha (4)-, and alpha (5)-integrin. In comparison with eutopic endometrium, ectopic endometrium shows reduced expression of alpha (2)- and alpha (v)-integrin. Since no differences in alpha (2)- and alpha (v)-integrin expression were observed in eutopic endometrium between endometriosis patients and control individuals, it may be suspected that the reduced expression of these in ectopic endometrium is explained by influences in the altered environment -- e. g., in the peritoneal fluid -- on the ectopic endometrium.

Biopsy↗

PubMed2006

[Identification of preeclampsia by cDNA-gene expression profiling in human placentas and serum -- a pilot study].

OBJECTIVE: Preeclampsia is associated with significant maternal and fetal morbidity and mortality. The etiology remains unclear. For the accurate diagnosis and the prevention of preeclampsia it seems to be important to find a diagnostic tool that identifies risk patients before symptoms occur. With a new approach, the cDNA-Array analysis, human placentas and blood from preeclamptic and healthy pregnant women were examined for differentially expressed genes to find typical genes expression profiles. MATERIAL AND METHODS: In this pilot study, cDNA array analysis with a 19 200 gene array of placenta and blood samples from three preeclamptic patients have been performed to classify this samples based on expression patterns. RESULTS: Comparing normal placenta and blood from healthy delivered women (n = 4), a subset of 200 genes repeatedly found to be differentially expressed in preeclampsia. The placenta and blood samples from preeclampsia were accurately grouped by their individual gene expression patterns. CONCLUSIONS: These results suggest that the use of cDNA array is a tool to identify gene expression patterns in preeclampsia. With this set of differentially expressed genes in conjunction with sample clustering algorithms the identification of preeclampsia in placenta or blood samples is possible.

Adult↗

PubMed2006

[Management of abnormal uterine bleeding].

Bleeding disorders are one of the most frequent gynecological problems. The causes of bleeding disorders, and their frequency in particular, vary depending on the age of the woman affected. In premenopause and perimenopause, the most frequent causes are hormonal, in up to 90 % of cases, as well as organic changes in the uterus such as myomas, adenomyosis uteri, or endometrial polyps, in up to 70 % of cases. Coagulation defects cause increased bleeding, particularly in girls and young women, with no other recognizable cause. The treatment of bleeding disorders is causally based, although if the woman does not wish to have children, the therapeutic algorithm in many cases leads to similar symptomatic measures. The following therapeutic approaches, listed in order of increasing efficacy, are mainly used in the treatment of increased bleeding: gestagen, estrogen-gestagen combination, levonorgestrel (Mirena) and endometrial ablation or myoma enucleation, with comparable success rates, and finally hysterectomy. Embolization of the uterine artery in myomas or adenomyosis uteri, nonsteroidal anti-inflammatory drugs, and antifibrinolytic agents represent alternatives that may be useful in individual cases. The paper provides an overview of the various causes, useful diagnostic measures, and treatment options in uterine bleeding disorders.

Algorithms↗

PubMed2006

[Cervical cancer screening of HIV-positive women: is a prolongation of the screening interval meaningful?].

OBJECTIVE: Cervical cancer screening guidelines stated recently that the screening interval of healthy women can be extended up to 3 years. Can those recommendations be applied for high risk populations? MATERIAL AND METHODS: In a prospective setting 305 HIV-positive women have been enrolled in this analysis between September 2000 and December 2003. Patients have been characterized according to HPV (human papilloma virus) prevalence, CIN (cervical intraepithelial neoplasia) incidence and CD4 cell count. RESULTS: 41 % of all HIV-positive women were HPV positive (oncogene subtypes). In patients with diminished CD4 cells the HPV prevalence increased to 60 % (54/90). CIN was found in 27 % (83/305) women. CIN was more frequent by HPV-positive women with a CD4 cell count < 200 mm (3) (52 %, 38/72). The CIN incidence was also high in HIV-positive women with negative HPV infection and diminished CD4 cell count (39 %, 7/18 vs.7 %, 11/161). CONCLUSIONS: The current cervical cancer screening guidelines are not helpful in HIV-positive women. The CIN incidence is significantly higher as in the HIV-positive population. For this reason this high risk population as e. g. HIV-infected women need an intensive care of diagnostic tools and short screening intervals to detect CIN.

Adolescent↗

PubMed2006

[Case report -- needle in the breast].

A case of a 23-year-old, foreign language speaking patient is reported, who presented herself in our out-patient clinic with stitching pain in the upper left quadrant of her left breast. Not until the third appointment and intensive questioning, leading to more detailed informations about the medical history, it was possible to diagnose a sewing needle in the breast by mammography. Neither clinical signs nor several ultrasound examinations lead to the diagnosis before.

Adult↗

PubMed2006

[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006].

This years ASCO-meeting reinforced the trend of the recent years to get off from empirical treatment concepts to tailored and individualized diagnostics and therapy. However, the basis for an individual therapy is a specific molecular diagnostic which can be reflected in the analysis of hormonal receptor, HER-1, HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only able to prognosticate the course of disease but they also can predict the success of specific treatment approaches. Trastuzumab is standard therapy in HER-2 positive breast cancer both in the adjuvant and palliative setting. But new therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2 positive breast cancer even if trastuzumab is failing. Otherwise it might possibly be an alternative option but adequate clinical results have to be awaited. The targeted inactivation of EGFR-related signal transduction pathways by e. g. gefitinib did not show a substantial improvement neither as a single agent nor in combination with endocrine treatment. However, the appropriate subgroup which might benefit from this therapy has to be defined even if molecular data suggest that patients with ER positive and PR negative breast cancer might be such a group. The increasing knowledge in terms of the biology of bone metastasis led to the development of new treatment options as e. g. denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant cytotoxic treatment trials revealed that taxanes improve the prognosis of node positive breast cancer and should be administered sequentially. The advantage of switching to an aromatase inhibitor after two to three years of tamoxifen in endocrine treatment of postmenopausal patients is proved by two clinical trials (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to be evident that new targeted therapy options are effective and will set new standards for the treatment of breast cancer patients in the near future. The presentation for the ovarian cancer focused on the addition of a third cytotoxic agent to carboplatin and paclitaxel as the standard therapy for the primary treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary and recurrent ovarian cancer were presented. However, this is not yet a standard treatment for all patients and needs further investigations within large, multicentre, randomised trials. The lymphonodectomy as part of the primary therapy of the endometrial cancer seems to be a benefit at least in patients with advanced disease or high risk stage I tumours. The adjuvant therapy of uterine sarcomas is still not yet very well investigated and clear. A trial which recruited 12 years demonstrated a benefit in overall survival which has to be interpreted with caution. In this year again there have been registered an increasing number of interesting contributions from Germany, which also received international attention.

Biomarkers, Tumor↗

PubMed2006

[Risk factors for recurrence of vulvar intraepithelial neoplasia III (VIN III)].

OBJECTIVE: The incidence of vulvar intraepithelial neoplasia (VIN) has increased in the last decades. The therapy of VIN is the in toto resection. Still some patients develop VIN recurrence. The aim of this retrospective study is the identification of risk factors for VIN recurrence. MATERIAL AND METHODS: 68 Patients with VIN III has been examined in an univariate and multivariate analysis for the following parameters (follow-up: median 27 months): age, HPV, HIV, multicentricity, resection margins (1-4 mm, 5-9 mm, > or = 10 mm). RESULTS: In the univariate analysis positive HPV and HIV status correlated with VIN recurrence. Also resection margins < 5 mm showed a significant correlation with VIN recurrence. Multivariate analysis demonstrated that HPV, HIV and resection margins < 5 mm are independent risk factors. No statistically association was found for age and multicentricity. CONCLUSION: The aim of VIN therapy must be the total resection with a negative resection margin of > or = 5 mm. HPV- and/or HIV-positive patients have a significantly higher risk for VIN recurrence and need therefore an intensive follow up.

Adult↗

PubMed2006

[PTHrP and bone sialoprotein as prognostic markers for developing bone metastases in breast cancer patients].

BACKGROUND: Bone metastases belong to the most frequent metastases in breast cancer. Currently there exist no serum markers which allow early detection of bone metastases. PATIENTS AND METHODS: 89 patients with primary breast cancer have been investigated for parathyroid-hormone-related peptide (PTHrP) in the tumour and bone sialoprotein (BSP) in the serum. Both markers have been correlated with classical prognostic factors and survival. RESULTS: The median age of the patients was 56 years. 17 of the 89 patients developed bone metastases and 25 died during the observation period of 5 years. PTHrP correlated significantly with bone metastases free survival (p = 0.0004) and overall survival (p = 0.0005), whereas BSP correlated only with the bone metastases free survival (p = 0.03). Both markers were shown to be independent prognostic factors for the bone metastases free survival in the multivariate analysis. PTHrP was also found to be an independent prognostic factor for the overall survival. CONCLUSION: The investigation of PTHrP could be a prognostic marker for the presence of bone metastases while BSP could be a marker for the early detection of bone metastases.

Biomarkers, Tumor↗